Expansion in CD39(+) CD4(+) Immunoregulatory T Cells and Rarity of Th17 Cells in HTLV-1 Infected Patients Is Associated with Neurological Complications

Expansion in CD39(+) CD4(+) Immunoregulatory T Cells and Rarity of Th17 Cells in HTLV-1 Infected Patients Is Associated with Neurological Complications

Author Leal, Fabio E. Google Scholar
Ndhlovu, Lishomwa C. Google Scholar
Hasenkrug, Aaron M. Google Scholar
Bruno, Fernanda R. Google Scholar
Carvalho, Karina I. Google Scholar
Wynn-Williams, Harry Google Scholar
Kleine Neto, Walter Autor UNIFESP Google Scholar
Sanabani, Sabri S. Google Scholar
Segurado, Aluisio C. Google Scholar
Nixon, Douglas F. Google Scholar
Kallas, Esper Georges Autor UNIFESP Google Scholar
Institution Univ Calif San Francisco
Univ Hawaii
Universidade de São Paulo (USP)
Funcacao Prosangue
Universidade Federal de São Paulo (UNIFESP)
Abstract HTLV-1 infection is associated with several inflammatory disorders, including the neurodegenerative condition HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). It is unclear why a minority of infected subjects develops HAM/TSP. CD4(+) T cells are the main target of infection and play a pivotal role in regulating immunity to HTLV and are hypothesized to participate in the pathogenesis of HAM/TSP. the CD39 ectonucleotidase receptor is expressed on CD4(+) T cells and based on co-expression with CD25, marks T cells with distinct regulatory (CD39(+)CD25(+)) and effector (CD39(+)CD25(-)) function. Here, we investigated the expression of CD39 on CD4(+) T cells from a cohort of HAM/TSP patients, HTLV-1 asymptomatic carriers (AC), and matched uninfected controls. the frequency of CD39(+)CD4(+) T cells was increased in HTLV-1 infected patients, regardless of clinical status. More importantly, the proportion of the immunostimulatory CD39(+)CD25(-) CD4+ T-cell subset was significantly elevated in HAM/TSP patients as compared to AC and phenotypically had lower levels of the immunoinhibitory receptor, PD-1. We saw no difference in the frequency of CD39(+)CD25(+) regulatory (Treg) cells between AC and HAM/TSP patients. However, these cells transition from being anergic to displaying a polyfunctional cytokine response following HTLV-1 infection. CD39(-)CD25(+) T cell subsets predominantly secreted the inflammatory cytokine IL-17. We found that HAM/TSP patients had significantly fewer numbers of IL-17 secreting CD4(+) T cells compared to uninfected controls. Taken together, we show that the expression of CD39 is upregulated on CD4(+) T cells HAM/TSP patients. This upregulation may play a role in the development of the proinflammatory milieu through pathways both distinct and separate among the different CD39 T cell subsets. CD39 upregulation may therefore serve as a surrogate diagnostic marker of progression and could potentially be a target for interventions to reduce the development of HAM/TSP.
Language English
Sponsor National Institute of Allergies and Infectious Diseases
National Institutes of Health
University of California
San Francisco-Gladstone Institute of Virology & Immunology Center for AIDS Research
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
John E. Fogarty International Center
National Center for Research Resources
National Institute of General Medical Sciences from the National Institutes of Health
Grant number San Francisco-Gladstone Institute of Virology & Immunology Center for AIDS Research: P30 AI027763
FAPESP: 04/15856-9/Kallas
FAPESP: 2010/05845-0/Kallas
FAPESP: 11/12297-2/Sanabani
John E. Fogarty International Center: D43 TW00003
National Center for Research Resources: 5P20RR016467-11
National Institute of General Medical Sciences from the National Institutes of Health: 8P20GM103466-11
Date 2013-02-01
Published in Plos Neglected Tropical Diseases. San Francisco: Public Library Science, v. 7, n. 2, 15 p., 2013.
ISSN 1935-2735 (Sherpa/Romeo, impact factor)
Publisher Public Library Science
Extent 15
Origin http://dx.doi.org/10.1371/journal.pntd.0002028
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000315644900006
URI http://repositorio.unifesp.br/handle/11600/35900

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